A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01263704
Recruitment Status : Completed
First Posted : December 21, 2010
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This single arm, open-label study will assess the safety and efficacy of low dose fludarabine and cyclophosphamide in combination with standard dose MabThera/Rituxan (rituximab) as primary therapy in elderly patients (>/= 65 years) with chronic lymphocytic leukemia. Patients will receive six 28-day cycles of treatment with Mabthera/Rituxan (375 mg/m2 intravenously [iv] Day 0 of cycle 1, 500 mg/m2 iv Day 1 of cycles 2-6), fludarabine (12.5 mg/m2/d iv Days 1-3, cycles 1-6) and cyclophosphamide (150 mg/m2/d iv Days 1-3, cycles 1-6). Anticipated time on study treatment is 6 months, with a 30-month follow-up period.

Condition or disease Intervention/treatment Phase
Lymphocytic Leukemia, Chronic Drug: Cyclophosphamide Drug: Fludarabine Drug: Rituximab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single Arm Study to Determine the Efficacy and Safety of Low Dose Fludarabine and Cyclophosphamide Combined With Standard Dose Rituximab as Primary Therapy in Elderly Untreated Patients (>/=65 Years Old) With Chronic Lymphocytic Leukemia
Actual Study Start Date : July 17, 2011
Actual Primary Completion Date : April 3, 2017
Actual Study Completion Date : April 3, 2017

Arm Intervention/treatment
Experimental: Rituximab plus Fludarabine and Cyclophosphamide
Elderly participants with chronic lymphocytic leukemia (CLL) will receive combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment is followed by a follow up period of 36 months.
Drug: Cyclophosphamide
150 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1-3 of each 28-day cycle for 6 cycles

Drug: Fludarabine
12.5 mg/m^2 IV on Days 1-3 of every 28-day cycle for 6 cycles

Drug: Rituximab
375 mg/m^2 IV Day 0 of Cycle 1, 500 mg/m^2 IV Day 1 of Cycles 2-6. Each cycle was 28 days.
Other Name: MabThera/Rituxan

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 42 months ]
    Overall response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to National Cancer Institute - Working Group [NCI-WG] guidelines. CR: no clonal B lymphocytes in peripheral blood, no significant lymphadenopathy, liver and spleen normal size, no disease symptoms, blood counts: absolute neutrophil count (ANC) >1,500/microliter (mcL), platelets > 100,000/mcL, hemoglobin > 11.0 grams/deciliter (g/dL), normocellular bone marrow. PR: >/= 50% decrease in clonal B lymphocyte count, >/= 50% reduction in lymphadenopathy, >/= 50% reduction of liver or spleen enlargement and ANC >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 11.0 g/dL OR >/= 50% increase in ANC, platelets or hemoglobin.

Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 53 months ]
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Preexisting conditions which worsen during a study are also considered as adverse events. An SAE is any experience that suggests a significant hazard, contraindication, side effect, or precaution, and fulfills any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

  2. Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations [ Time Frame: Up to 53 months ]
  3. Hospitalization Days [ Time Frame: Up to 53 months ]
  4. Progression-free Survival (PFS) [ Time Frame: Up to 53 months ]
    PFS was defined as the interval from the first study drug treatment day to the first sign of disease progression according to NCI-WG guidelines. Progressive disease (PD): Any new lesion, any disease symptoms, >/=50% increase in lymphadenopathy, splenomegaly, hepatomegaly, >/= 50% increase in the number of circulating clonal B lymphocytes, decrease of hemoglobin levels by > 2.0 g/dL, >/= 50% decrease of platelet counts, increase of lymphocytes in bone marrow to more than 30% from normal.

  5. Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire [ Time Frame: [Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)] ]
    The FACIT-F questionnaire consists of 13 questions with a total score range of 0 to 52 with 0 indicating a better outcome and 52 indicating a worse outcome.

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients, >/= 65 years of age
  • Previously untreated B-cell chronic lymphocytic leukemia (CLL)
  • Binet stage C or active Binet stage A and B disease

Exclusion Criteria:

  • Prior treatment for CLL
  • CLL with transformation (Richter's syndrome)
  • Suspected or known central nervous system (CNS) involvement of CLL
  • Impaired renal or hepatic function
  • Human Immunodeficiency Virus (HIV) positivity, active hepatitis B/C or Hepatitis B Virus (HBV) surface antigen positive, or any active or uncontrolled infections
  • Patients with anti-HBV core antibodies (past infection with HBV) but who are negative for Hepatitis B Virus Surface Antigen (HBVsAg) (either anti-HBS Ab positive or negative) and are positive for HBV- Deoxyribonucleic acid (DNA) by Polymerase chain reaction (PCR) analysis
  • Concomitant diseases requiring chronic steroid administration
  • Active second malignancy within the 2 years prior to study (except for non-melanoma skin cancer and in situ cervix or breast or prostate carcinoma)
  • Eastern Cooperative Oncology Group (ECOG) performance status >/= 3

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01263704

Haemek Medical Center; Hematology Department
Afula, Israel, 18101
Soroka Medical Center; Hematology Deptartment
Beer Sheva, Israel, 8410101
Rambam Medical Center; Heamatology & Bone Marrow Transplantation
Haifa, Israel, 3109601
Bnei-Zion Medical Center; Hematology Dept
Haifa, Israel, 3339419
Shaare Zedek Medical Center; Hematology Dept.
Jerusalem, Israel, 9103102
Hadassah Ein Karem Hospital; Haematology
Jerusalem, Israel, 9112001
Meir Medical Center; Internal Dept A
Kfar Saba, Israel, 44281
Western Galilee Hospital - Nahariya
Nahariya, Israel, 22100
Beilinson Medical Center; Haematology
Petach Tikva, Israel, 49100
Kaplan Medical Center
Rehovot, Israel, 7661041
ASSAF Harofe; Department of Hematology
Rishon Lezion, Israel, 70300
Ichilov Sourasky Medical Center; Heamatology
Tel Aviv, Israel, 6423906
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Responsible Party: Hoffmann-La Roche Identifier: NCT01263704     History of Changes
Other Study ID Numbers: ML25464
First Posted: December 21, 2010    Key Record Dates
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents